Error Negativity Does Not Reflect Conflict: A Reappraisal of Conflict Monitoring and Anterior Cingulate Cortex Activity

Our ability to detect and correct errors is essential for our adaptive behavior. The conflict-loop theory states that the anterior cingulate cortex (ACC) plays a key role in detecting the need to increase control through conflict monitoring. Such monitoring is assumed to manifest itself in an electroencephalographic (EEG) component, the "error negativity" (Ne or "error-related negativity" [ERN]). We have directly tested the hypothesis that the ACC monitors conflict through simulation and experimental studies. Both the simulated and EEG traces were sorted, on a trial-by-trial basis, as a function of the degree of conflict, measured as the temporal overlap between incorrect and correct response activations. The simulations clearly show that conflict increases as temporal overlap between response activation increases, whereas the experimental results demonstrate that the amplitude of the Ne decreases as temporal overlap increases, suggesting that the ACC does not monitor conflict. At a functional level, the results show that the duration of the Ne depends on the time needed to correct (partial) errors, revealing an "on-line" modulation of control on a very short time scale

Renewing accessible heptazine chemistry: 2,5,8-tris(3,5-diethyl-pyrazolyl)-heptazine, a new highly soluble heptazine derivative with exchangeable groups, and examples of newly derived heptazines and their physical chemistry

International audienceWe have prepared 2,5,8-tris(3,5-diethyl-pyrazolyl)-heptazine, the first highly soluble heptazine derivative possessing easily exchangeable leaving groups. We present its original synthesis employing mechanochemistry, along with a few examples of its versatile reactivity. It is, in particular, demonstrated that the pyrazolyl leaving groups can be replaced by several secondary or primary amino substituents or by three aryl-or benzyl-thiol substituents. In addition to being a synthetic platform, 2,5,8-tris(3,5-diethyl-pyrazolyl)-heptazine is fluorescent and electroactive, and its attractive properties, as well as those of the derived heptazines, are briefly presented

Fast 3D Microscopy Imaging of Contacts Between Surfaces Using a Fluorescent Liquid

International audienceA novel method is presented for the rapid direct 3D visualization of the contact between two surfaces by means of fluorescence microscopy using a fluorescent liquid. Distances between the surfaces of up to several hundred nanometers can be determined with subnanometer accuracy in 3D and within seconds of measurement time. The method opens new possibilities for research in the areas of contact mechanics, friction, wear, and lubrication

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Sondes fluorescentes pour l'ADN : marquages covalent et non-covalent.

Fluorescent labelling of biomolecules has become increasingly important for biological studies. In this context, we designed new probes for covalent and non-covalent labelling of DNA.The non covalent approach was based on structural recognition principles and made use of G4-DNA as target. The mixed properties of conjugates comprised of a G4-binder motif and of a fluorescent label prompted us to use Thiazole Orange (TO). TO binds G4-DNA with a high affinity and exhibits a strong fluorescence exaltation. Thus, affinities of G4-binders can be evaluated by competitive displacement of this probe. It was also shown that G4-DNA represents a scaffold for energy transfer (FRET) between a G4-binder and TO.The covalent approach was based on the design of small-sized derivatizable fluorescent probes with two photon absorption properties. Some of these derivatives show a strong fluorescent exaltation in presence of DNA and two photon absorption properties stronger than usual biological dyes.Le marquage fluorescent de biomolécules est devenu un outil incontournable en biologie. Dans ce contexte, nous avons conçu de nouvelles sondes fluorescentes pour l'ADN.Le marquage non-covalent d'ADN quadruplexe (ADN-G4) par reconnaissance structurale a été étudié. Les propriétés mitigées des composés obtenus en conjuguant un ligand d'ADN-G4 à des sondes fluorescentes nous ont conduit à étudier le Thiazole Orange (TO), dont la fluorescence est exaltée par l'ADN. Le TO a une forte affinité pour l'ADN-G4, qui exalte fortement sa fluorescence. L'affinité d'un ligand d'ADN-G4 peut donc être évaluée par déplacement compétitif de cette sonde. De plus, l'ADN-G4 constitue une matrice favorisant le transfert d'énergie entre un ligand de G4 et le TO.Des sondes de taille réduite, avec une forte absorption biphotonique et permettant le marquage covalent d'ADN ont ensuite été développées. Certaines de ces sondes présentent une exaltation de fluorescence en présence d'ADN

Sondes fluorescentes pour l'ADN (marquage covalent et non-covalent)

Le marquage fluorescent de biomolécules est devenu un outil incontournable en biologie. Dans ce contexte, nous avons conçu de nouvelles sondes fluorescentes pour l ADN. Le marquage non-covalent d ADN quadruplexe (ADN-G4) par reconnaissance structurale a été étudié. Les propriétés mitigées des composés obtenus en conjuguant un ligand d ADN-G4 à des sondes fluorescentes nous ont conduit à étudier le Thiazole Orange (TO), dont la fluorescence est exaltée par l ADN. Le TO a une forte affinité pour l ADN-G4, qui exalte fortement sa fluorescence. L affinité d un ligand d ADN-G4 peut donc être évaluée par déplacement compétitif de cette sonde. De plus, l ADN-G4 constitue une matrice favorisant le transfert d énergie entre un ligand de G4 et le TO. Des sondes de taille réduite, avec une forte absorption biphotonique et permettant le marquage covalent d ADN ont ensuite été développées. Certaines de ces sondes présentent une exaltation de fluorescence en présence d ADN.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Analyse critique des réformes de la réglementation de la distribution française

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β-Diketone derivatives: influence of the chelating group on the photophysical and mechanofluorochromic properties

International audienceA diphenyl-boron β-diketonate complex was synthesized. Its photophysical properties were studied in solution and in the solid-state, and compared to those of its parent diketone and the corresponding difluoro-boron complex. TD-DFT calculations show that the molecular orbitals involved in the first Franck–Condon transition are very different for the three compounds studied. The difluoro-boron complex is strongly fluorescent in solution, and remains fluorescent in the solid-state. The free diketone turns to be very weakly fluorescent in solution and displays significant Aggregation Induced Enhanced Emission (AIEE) in the crystalline state, which can be explained by a rigidification of the molecule, while the diphenyl-boron complex is weakly fluorescent in solution as well as in the solid-state. For the free di-ketone and the difluoro-boron complex a mechanofluorochromic response is observed upon grinding the crystalline powder in a mortar, while for the diphenyl-boron complex no fluorescence emission change is detected under these conditions. Overall, this study shows that the nature of the chelating group has a crucial influence on the photophysical and mechanofluorochromic properties of β-diketonate complexes, leading to a wide variety of behaviors within the closely related structures of such derivatives

Tetrazine-functionalized and vertically-aligned mesoporous silica films with electrochemical activity and fluorescence properties

International audienceIn spite of their attractive physico-chemical properties making them very promising in the field of functional molecular materials, s-tetrazine derivatives remain underexploited in practical devices mainly because their immobilization in a stable form maintaining all their features is still challenging. Here, we show that combining a `click chemistry azide/alkyne' approach with an electrochemically-assisted self-assembly (EASA) method, which is likely to generate azide-functionalized and vertically-aligned mesoporous silica films, and further derivatization of the ordered mesoporous material with propargyl-tetrazine via a soft Huisgen coupling reaction, enable one to reach this goal. The resulting tetrazine-functionalized films formed onto transparent indium-tin oxide (ITO) electrodes exhibit well-defined voltammetric signals, with peak currents proportional to the functionalization level and stable upon multiple potential scanning, as well as effective fluorescence properties as evidenced from fluorescence spectra with maximum emission at 555-560 nm